Lam B K, Yang C Y, Wong P Y
Department of Physiology, New York Medical College, Valhalla.
Adv Exp Med Biol. 1990;275:183-91. doi: 10.1007/978-1-4684-5805-3_12.
High levels of soluble phospholipase A2 (PLA2) activity have been detected in tissues fluids associated with inflammatory diseases. However, the cellular origin for PLA2 has not been demonstrated. Several groups of investigators have proposed that platelets, macrophages and chondrocytes may be the cellular source of this enzyme. In fact, soluble PLA2 is secreted extracellularly from rabbit and rat chondrocytes and from human synovial cells in response to cytokine stimulation (1). PLA2 activity has been shown to be increased upon stimulation by the chemotactic peptide (f-met-leu-phe) and thrombin in neutrophils and platelets (2). PLA2 has been found to have pro-inflammatory effects and causes a dose dependent infiltration of leukocytes and increased vascular permeability (3). The vascular actions of PLA2 have been proposed to be mediated through the release of prostaglandin E2 and thromboxane (4). We have reported that purified PLA2 from snake venom stimulated the release of leukotrienes and lipoxins from endogenous sources in porcine leukocytes. However, there is no information regarding the mechanism of action of human PLA2 on inflammatory cells and the generation of leukotrienes. In this report, we present evidence that PLA2 isolated from human platelets can stimulate the production of leukotriene B4 from human polymorphonuclear leukocytes. These results suggest that soluble PLA2 may function as a secretagogue of LTB4 in inflammatory sites and further amplify the inflammatory processes by inducing chemotaxis of circulating leukocytes.
在与炎症性疾病相关的组织液中已检测到高水平的可溶性磷脂酶A2（PLA2）活性。然而，PLA2的细胞来源尚未得到证实。几组研究人员提出，血小板、巨噬细胞和软骨细胞可能是这种酶的细胞来源。事实上，可溶性PLA2是兔和大鼠软骨细胞以及人滑膜细胞在细胞因子刺激下分泌到细胞外的（1）。在中性粒细胞和血小板中，PLA2活性已被证明在趋化肽（f-甲硫-亮-苯丙）和凝血酶刺激下会增加（2）。已发现PLA2具有促炎作用，并导致白细胞剂量依赖性浸润和血管通透性增加（3）。有人提出PLA2的血管作用是通过前列腺素E2和血栓素的释放介导的（4）。我们曾报道，从蛇毒中纯化的PLA2刺激猪白细胞内源性来源释放白三烯和脂氧素。然而，关于人PLA2对炎症细胞的作用机制以及白三烯的产生尚无相关信息。在本报告中，我们提供证据表明，从人血小板中分离出的PLA2可以刺激人多形核白细胞产生白三烯B4。这些结果表明，可溶性PLA2可能在炎症部位作为白三烯B4的促分泌素发挥作用，并通过诱导循环白细胞趋化进一步放大炎症过程。
